The cGMP-dependent channel of vertebrate rod photoreceptors exists in two forms of different cGMP sensitivity and pharmacological behavior.

Abstract

cGMP cooperatively activates a cation-selective channel in vertebrate photoreceptors probably by direct binding to a membrane receptor (Fesenko, E. E., Kolesnikov, S. S., and Lyubarsky, A.L. (1985) Nature 313, 310-313). We have recently described the existence of a similar channel in photoreceptor disc membranes (Koch, K. W., and Kaupp, U. B. (1985) J. Biol. Chem. 260, 6788-6800). In this paper we report that the cGMP-dependent channel in the disc membrane of outer segments exists in at least two forms of different cGMP sensitivity and pharmacological behavior. One form has a low Km value of activation by cGMP (25 microM), and it is not blocked by l-cis-diltiazem. The other form has a high Km value (170 microM) and is blocked by this drug. Both channel forms are cooperatively activated by cGMP (Hill coefficient n = 2.0-3.5), suggesting that the channel may have a cGMP receptor that can bind at least three, and possibly four, molecules of cGMP. In the presence of cGMP, the open state of both channel forms inactivates to a weakly or nonconductive state (cf. Puckett, K. L., and Goldin, S. M. (1986) Biochemistry 25, 1739-1746). A mixed population of different forms of the cGMP-dependent channel may explain the variable numbers reported for the Michaelis constant Km for the channel activation by cGMP and the cooperativity n.